1. Description of the problem

Acute respiratory failure is common in the pediatric and neonatal intensive care units. When traditional mechanical ventilation techniques fail, extracorporeal membrane oxygenation (ECMO) can provide temporary, life saving, respiratory support. ECMO is provided only to a select group of patients with a high mortality risk (>75%). Overall survival to discharge of neonatal respiratory ECMO patients are 75% and 56% for pediatric respiratory ECMO cases.

The procedure

ECMO for respiratory failure can be provided almost universally utilizing a veno-venous approach. This avoids many of the negative features of veno-arterial ECMO including need for carotid ligation, risk of systemic thromboembolism, and increased native cardiac afterload. Surgery is required to place the ECMO cannulas, usually in the internal jugular or femoral veins. Double lumen cannulas are available and enable single vascular site access for many patients. In the simplest implementation, blood exits the body through the drainage cannula and will be driven through the extracorporeal circuit via a pump. Both roller head and centrifugal pump designs are commonly used in ECMO with distinct strengths and weaknesses. The blood is then driven through an oxygenator, which provides the gas exchange function of the lung (CO2 removal and O2 delivery). Oxygenators vary by design and materials, but all share the concept of having a thin membrane that physically separates the blood phase from the gas phase, but allows gas transfer between the two compartments. The newly oxygenated and CO2- deprived blood is returned to the patient via a return cannula. In veno-venous ECMO, there is no direct cardiac support. The physiology is similar to normal physiology, with the exception that you have oxygenated blood in the right ventricle and pulmonary arteries.

Veno-arterial ECMO can provide both respiratory and cardiac support. In this implementation, the drainage cannula is placed in a large vein (IJ or femoral), and the return cannula is placed into the carotid artery. The physiology of veno-arterial ECMO is more complex and is similar to what occurs in the setting of cardiopulmonary bypass in the operating room.

Patients must receive anticoagulation while receiving ECMO therapy to prevent thrombosis within the extracorporeal circuit. This is typically accomplished using unfractionated heparin. Complications of thrombosis (inadequate anticoagulation) and hemorrhage (excessive anticoagulation) are common during ECMO, and frequent monitoring of the coagulation system is required. Activated clotting times are measured hourly at bedside, with a more generalized evaluation of the coagulation system (platelet count, PT, aPTT, etc.) performed at least once a day. Continuous monitoring of pressures and blood flow at multiple points in the extracorporeal circuit are necessary to ensure safe usage of the ECMO system. Often, the management of the ECMO circuit alone requires a separate and dedicated trained personnel on top of the nursing and respiratory care needs of the patient. Patient- and disease-specific guidelines are provided on the Extracorporeal Life Support (ELSO) website at http://www.elso.med.umich.edu. Average duration of ECMO therapy is approximately 9 days for the neonates and 12 days for the pediatric patients.

Early identification of ECMO candidates is essential for optimizing outcomes. Consultation with an ECMO center to facilitate transfer and medical management is recommended. A list of ECMO centers and contact information is available at the ELSO website at http://www.elso.med.umich.edu.

2. Emergency Management

Initial stabilization

These patients are always critically ill and often quite unstable. General recommendations for resuscitation and treatment of the underlying cause of their disease, if known, should be instituted. Provide adequate oxygenation and ventilation to these patients using traditional mechanical support. The clinical focus should be on global oxygen delivery to the patient, not solely the patients arterial saturation. Techniques that improve oxygen delivery, such as transfusion of packed red blood cells to maximize oxygen-carrying content and delivery of inotropes to improve cardiac output, should be considered. If needed, use of advanced ventilatory techniques, such as high-frequency oscillating ventilation, recruitment maneuvers, prone positioning, or a trial of 20ppm of inhaled nitric oxide may aid in stabilization.

Patient managment

Therapy for underlying cause should be provided if known. If infectious causes are considered, broad empiric antimicrobial coverage is indicated, but should be narrowed once a specific etiologic agent is found. Placement of multiple indwelling venous and arterial catheters is often helpful in managing these critically ill children and can aid in providing targets for goal-directed therapies. Sedation and paralysis are often necessary in the management of these patients. Any invasive procedures that are anticipated should be performed prior to ECMO by the most skilled practitioner available and with a particular emphasis on hemostasis.

ECMO Consultation

As described above, early identification of patients is essential to good outcomes. Contact the nearest ECMO center and have available:

The oxygen index is a valuable tool for helping to determine those patients with severe lung disease and a high risk of mortality that may benefit from ECMO. The oxygen index is calculated as the FiO2 x mean airway pressure (MAP) x 100 divided by the paO2. Historically, an oxygen index greater than 40 is associated with greater than 80% mortality and an oxygen index of 25 to -40 is associated with 50% to 80% mortality.

3. Diagnosis

Severe lung injury necessitating ECMO does not have a specific set of criteria that applies uniformly to every patient. Again, these are rare patients, and when all of the standard critical care tactics are not being successful, that is the primary indication to call an ECMO center. Additionally, patients who are on very high ventilator settings but are stable and not expected to improve in 1 to 2 weeks are also considered candidates. Indications for ECMO consultation in the neonatal population include an oxygen index greater than 40, or greater than 25 for 6 hours. In the pediatric population, ECMO consultation would be reasonable for any patient with an oxygen index greater than 25, mean airway pressure greater than 25, or a PEEP greater than 10 on FiO2 greater than 0.6.

Pathophysiology

Severe hypoxemic lung failure can be incited from a variety of direct and indirect insults. Direct causes of injury include infectious pneumonias, gastric aspiration events, pulmonary hemorrhage, and aspirations of toxic chemicals (hydrocarbons). Indirect causes of lung injury are pancreatitis, severe sepsis, and multiple organ dysfunction syndrome. Regardless of the etiology, all affect the lung's native gas exchange by a combination of direct alveolar injury, alveolar flooding, impairment of ventilation and perfusion matching, and thickening of the alveolar/capillary membrane.

ECMO functions as temporary support to the gas exchanging units of the lung by providing this function extracorporeally. It does nothing to cure the underlying disease, it only provides time for the native lung to heal and for additional therapies (such as antibiotics) to work. While on ECMO, the ventilator is turned down to very low settings to avoid additional ventilator induced lung injury. Often the lungs are completely opacified on chest radiographs in the first few days after ECMO institution. As the lung parenchyma heals and becomes more compliant, aeration will start to appear on the chest x-ray and it will gradually improve. In veno-venous applications, to test the patient's native lung function, the gas source can be removed from the oxygenator. In this scenario, all gas exchange is now occurring through the patient's own lungs. If reasonable gas exchange is achieved, then the cannulas can be removed and the patient liberated from ECMO. Recovery of native lung function may be prolonged, and no explicit maximum number of days on ECMO is recommended. Each patient should be evaluated individually. However, if a patient is not improving, then the difficult decision to remove ECMO and return to standard ventilatory techniques must be performed.

Epidemiology

Need for ECMO for either cardiac or respiratory indications is rare, however, use is increasing. The ELSO database contains the largest population of patients placed on ECMO. In 2009, 2766 patients were placed on ECMO. ECMO use is increasing in the adult population after successful use during the H1N1 influenza pandemic. The fastest growing population of ECMO patients are the patients with congenital cardiac lesions.

Approximately 24,000 neonates have been supported with ECMO for respiratory failure with 75% survival to discharge. Neonatal diseases with good prognosis include meconium aspiration syndrome (94% survival) and respiratory distress syndrome (84%). Congenital diaphragmatic hernia outcomes remain at approximately 50% survival. With the advent of advanced mechanical ventilation strategies, the use of high-frequency oscillating ventilators and inhaled nitric oxide, respiratory ECMO use in the neonatal population is decreasing—from a peak of 1516 in 1992 to 696 cases in 2009.

Another 4700 pediatric patients have been supported with respiratory ECMO with 56% survival to discharge. Underlying diseases leading to severe lung failure in the pediatric population are much more diverse compared to the neonates. Co-morbidities are becoming more frequent as well. One population with 95% survival in the pediatric population is the use of extracorporeal gas exchange in severe hypercarbic respiratory failure from status asthmaticus that is unresponsive to all traditional therapies and inhaled anesthetic agents. Use of ECMO for the unremitting pulmonary hypertension and lung disease associated with pertussis remains difficult, with only 30% survival.